Writing in the journal Gut, the team report on findings from the U.S. Vitamin D/Calcium Polyp Prevention Study which was a chemopreventive trial originally designed to see if calcium (or calcium plus vitamin D) supplements reduced the likelihood of further pre-malignant bowel growths in people who had previously had a polyp removed.
However, the team behind the study were surprised to find the opposite effect.
Indeed, the use of calcium supplements alone led to a 2.5 fold increase in risk of pre-cancerous polyps known as SSAs (sessile serrated adenomas). Meanwhile, combined calcium and vitamin D supplementation resulted in nearly quadruple the risk.
Women and smokers were found to be at higher risk from exposure to calcium supplements.
However, there was no increase in risk associated with vitamin D supplements in isolation; nor was there any link between dietary calcium and increased polyp risk, the researchers noted.
The increase in risk of developing serrated polyps appeared to be a long-term effect with a substantial period of latency. In the treatment (supplementation) phase, there was no effect of either calcium (either with or without vitamin D) on the incidence of SSAs. However, the increased risk of SSAs became evident during bowel examinations following the subsequent observational stage, 3-5 years after the end of supplementation.
“Using data from a recently completed randomised chemoprevention trial of vitamin D and calcium in patients with colorectal adenomas, we found that calcium and the combination of calcium and vitamin D increased the risk of SSA/Ps 6–10 years after supplementation began,” commented lead author Seth D. Crockett, MD, from the University of North Carolina's Division of Gastroenterology and Hepatology.
The randomised controlled trial included 2259 individuals aged between 45-75 years from multiple centres in the U.S. All participants had previously undergone removal of an adenoma at baseline.
Patients were randomised to four main groups: 1200 milligrams / day (mg/d) of calcium plus 1000 IU/d of vitamin D3, calcium plus placebo, vitamin D plus placebo or placebo. Patients underwent surveillance colonoscopies after 3 or 5 years of supplementation (treatment phase), and again a further 3-5 years later (observation phase).
Various types of polyps can grow within the lower large bowel. Hyperplastic polyps (HP- a type of serrated polyp) are more common, but less likely to turn cancerous than the more advanced SSA type, explained the researchers.
Previous observational studies have found an inverse association between dietary calcium intake and risk of HP and SSA, while secondary analysis within this trial found no association.
“Taken together, our results would suggest that only calcium supplementation, not dietary calcium intake, is associated with SPs overall and SSA/Ps specifically,” observed the researchers.
Very little other data exists on the links between calcium supplementation and colorectal cancer arising from serrated polyps. The findings therefore justify further research to verify evidence from this trial, suggested the scientists.
“Further studies are recommended to confirm these results, which may have important implications for CRC screening and prevention,” concluded Crockett.
Meanwhile, “Patients with a history of premalignant serrated polyps, especially women and smokers, may wish to avoid vitamin D and calcium supplementation,” the researchers recommended.
Published Online First: 1 March 2018. DOI: 10.1136/gutjnl-2017-315242
“Calcium and vitamin D supplementation and increased risk of serrated polyps: results from a randomised clinical trial”
Authors: Seth D. Crockett et al